7-76510893-G-A

Variant names:

• chr7-76510893-G-A
• rs150340826
• NM_001347684.2:c.86-10G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001347684.2(UPK3B):​c.86-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,593,856 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (8 hom.)
• Consequence: UPK3B NM_001347684.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19
• Publications: 2 publications found

Genes affected

UPK3B (HGNC:21444): (uroplakin 3B) UPK3B is a minor component of the apical plaques of mammalian urothelium that binds and dimerizes with uroplakin-1b (UPK1B; MIM 602380), one of the major conserved urothelium membrane proteins. The other major conserved integral membrane proteins of urothelial plaques are UPK1A (MIM 611557), UPK2 (MIM 611558), and UPK3A (MIM 611559) (Deng et al., 2002 [PubMed 12446744]).[supplied by OMIM, Mar 2008]

ENSG00000297839 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004237652).
• BP6: Variant 7-76510893-G-A is Benign according to our data. Variant chr7-76510893-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3466296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347684.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3B	NM_001347684.2	MANE Select	c.86-10G>A		intron	N/A	NP_001334613.1	Q9BT76-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK3B	ENST00000334348.8	TSL:2 MANE Select	c.86-10G>A		intron	N/A	ENSP00000334938.3	Q9BT76-3
	UPK3B	ENST00000257632.9	TSL:2	c.241G>A	p.Val81Met	missense	Exon 1 of 4	ENSP00000257632.5	Q9BT76-1
	UPK3B	ENST00000911147.1		c.86-10G>A		intron	N/A	ENSP00000581206.1

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 152148 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00235

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00107 AC: 225 AN: 209554 AF XY: 0.00106

Gnomad AFR exome AF: 0.000471

Gnomad AMR exome AF: 0.000767

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.000949

GnomAD4 exome AF: 0.00210 AC: 3030 AN: 1441590 Hom.: 8 Cov.: 34 AF XY: 0.00207 AC XY: 1484 AN XY: 715782

African (AFR) AF: 0.000212 AC: 7 AN: 32988

American (AMR) AF: 0.000797 AC: 33 AN: 41418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25730

East Asian (EAS) AF: 0.00 AC: 0 AN: 38146

South Asian (SAS) AF: 0.0000717 AC: 6 AN: 83736

European-Finnish (FIN) AF: 0.000467 AC: 24 AN: 51434

Middle Eastern (MID) AF: 0.000387 AC: 2 AN: 5174

European-Non Finnish (NFE) AF: 0.00256 AC: 2829 AN: 1103406

Other (OTH) AF: 0.00217 AC: 129 AN: 59558

GnomAD4 genome AF: 0.00135 AC: 205 AN: 152266 Hom.: 1 Cov.: 32 AF XY: 0.00111 AC XY: 83 AN XY: 74460

African (AFR) AF: 0.000529 AC: 22 AN: 41564

American (AMR) AF: 0.000850 AC: 13 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00235 AC: 160 AN: 68004

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00173 Hom.: 2

Bravo AF: 0.00139

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.000870 AC: 105

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.058
DANN	Benign	0.86
DEOGEN2	Benign	0.00044	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.016
Sift	Benign	0.049	D
Sift4G	Benign	0.16	T
Polyphen		0.44	B
Vest4		0.018
MVP		0.014
ClinPred		0.0024	T
GERP RS		-6.0
PromoterAI		-0.0032	Neutral
Varity_R		0.026

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150340826; hg19: chr7-76140210;